rs387906493
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM4BP6_Very_StrongBS2
The NM_139058.3(ARX):βc.428_451delβ(p.Gly143_Ala150del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000176 in 794,928 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (β β ).
Frequency
Genomes: π 0.0000096 ( 0 hom., 0 hem., cov: 21)
Exomes π: 0.000019 ( 0 hom. 4 hem. )
Consequence
ARX
NM_139058.3 inframe_deletion
NM_139058.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.09
Genes affected
ARX (HGNC:18060): (aristaless related homeobox) This gene is a homeobox-containing gene expressed during development. The expressed protein contains two conserved domains, a C-peptide (or aristaless domain) and the prd-like class homeobox domain. It is a member of the group-II aristaless-related protein family whose members are expressed primarily in the central and/or peripheral nervous system. This gene is thought to be involved in CNS development. Expansion of a polyalanine tract and other mutations in this gene cause X-linked cognitive disability and epilepsy. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_139058.3.
BP6
?
Variant X-25013543-GCGGCCGCGGCTGCCGCGGCGGCCC-G is Benign according to our data. Variant chrX-25013543-GCGGCCGCGGCTGCCGCGGCGGCCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 1235070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High Hemizygotes in GnomAdExome4 at 4 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARX | NM_139058.3 | c.428_451del | p.Gly143_Ala150del | inframe_deletion | 2/5 | ENST00000379044.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARX | ENST00000379044.5 | c.428_451del | p.Gly143_Ala150del | inframe_deletion | 2/5 | 1 | NM_139058.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000959 AC: 1AN: 104289Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0AN XY: 29767
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GnomAD4 exome AF: 0.0000188 AC: 13AN: 690639Hom.: 0 AF XY: 0.0000191 AC XY: 4AN XY: 209747
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 10, 2020 | - - |
Intellectual disability, X-linked, with or without seizures, arx-related;C3463992:Developmental and epileptic encephalopathy, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2023 | - - |
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at